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Exercise training attenuates age-dependent elevation of angiotensin II type 1 receptor and Nox2 signaling in the rat heart

Title
Exercise training attenuates age-dependent elevation of angiotensin II type 1 receptor and Nox2 signaling in the rat heart
Author
김종희
Keywords
Aging; Heart; Angiotensin II receptor 1; NADPH oxidase; TGF-beta
Issue Date
2015-10
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
EXPERIMENTAL GERONTOLOGY, v. 70, Page. 163-173
Abstract
Fibrosis of the aging heart impedes cardiac function and increases the risk of arrhythmias and heart disease. Previously, we demonstrated that exercise-induced reduction of collagen I in the aging heart was linked to a suppression of oxidative stress and transforming growth factor-beta (TGF-beta). The renin-angiotensin II system (RAS) increases oxidative stress via NADPH oxidase-2 (Nox2) and thus elevates TGF-beta and collagen accumulation. Therefore, we tested the hypothesis that exercise training would alleviate age-related upregulation of the angiotensin II receptor I (AT1R) and NADPH oxidase-2 (Nox2), concomitant with suppression of TGF-beta and fibrosis. Young (3 months, n = 20) and old (31 months, n = 20) Fischer 344 x Brown Norway F1 (FBNF1) hybrid rats were assigned into sedentary and exercise groups, with exercise training rats training on a treadmill 45 min/day, 5 days/week for the next 12 weeks. Exercise training mitigated age-related upregulation of AT1R, Nox2 activity, and Nox2 subunits gp91phox and p47phox. Exercise training also attenuated TGF-beta positive staining and downstream effectors of fibrosis in the aging heart: connective tissue growth factor, phosphorylation of Smad2 at Ser423, myofibroblast proliferation, and collagen I-positive staining. Our results are consistent with the hypothesis that exercise training protects against age-dependent cardiac fibrosis by suppressing AT1R and Nox2 as part of a RAS-Nox2-TGF-beta pathway. (C) 2015 Elsevier Inc. All rights reserved.
URI
http://www.sciencedirect.com/science/article/pii/S0531556515300231?via%3Dihubhttp://hdl.handle.net/20.500.11754/28505
ISSN
0531-5565; 1873-6815
DOI
10.1016/j.exger.2015.07.016
Appears in Collections:
COLLEGE OF ART AND PHYSICAL EDUCATION[S](예술·체육대학) > PHYSICAL EDUCATION(체육학과) > Articles
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